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The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

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Abstract

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N = 1274; N = 829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N = 2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI] = 0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI] = 0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI] = 0.50 [0.25–0.99]); and remains significant (P = 0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

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Data availability

Raw data are available for collaboration purposes upon request at corresponding author.

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Funding

The study was supported by Ministry of Health of the Czech Republic, Grant NV18-01-00046; all rights reserved.

Author information

Authors and Affiliations

  1. Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague, 14021, Czech Republic

    Lucie Dlouha & Jaroslav A. Hubacek

  2. Diabetes Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague, 14021, Czech Republic

    Terezie Pelikanova, Jiří Veleba & Tomas Sosna

  3. Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague, 14021, Czech Republic

    Vera Adamkova

  4. Statistical Unit, Institute for Clinical and Experimental Medicine, Videnska 1958/9, Prague, 14021, Czech Republic

    Vera Lanska

  5. Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Vinicka 7, 12808, Prague, Czech Republic

    Lucie Dlouha

  6. Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 62500, Brno, Czech Republic

    Lukas Pacal & Katerina Kankova

  7. 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University, U Nemocnice 1, 12808, Prague, Czech Republic

    Jaroslav A. Hubacek

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  1. Lucie Dlouha
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  2. Terezie Pelikanova
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  3. Jiří Veleba
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  9. Jaroslav A. Hubacek
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection has been performed by PT, VJ, AV, ST, PL and KK. Genetic analysis were performed by DD, HJA. Statistical analyses performed LV. The first draft of the manuscript was written by HJA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jaroslav A. Hubacek.

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Not declared.

Ethical approval

The study protocol was approved by The Ethics Committee of the Institute for Clinical and Experimental medicine and Thomayer Hospital with multi-center competence and informed consent was signed by all study participants.

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Dlouha, L., Pelikanova, T., Veleba, J. et al. The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics. Mol Biol Rep 48, 5873–5879 (2021). https://doi.org/10.1007/s11033-021-06581-w

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